title: Integrative analysis of metabolomics and transcriptomics data: a unified model framework to identify underlying system pathways.
abstract: The abundance of high-dimensional measurements in the form of gene expression and mass spectroscopy calls for models to elucidate the underlying biological system. For widely studied organisms like yeast, it is possible to incorporate prior knowledge from a variety of databases, an approach used in several recent studies. However if such information is not available for a particular organism these methods fall short. In this paper we propose a statistical method that is applicable to a dataset consisting of Liquid Chromatography-Mass Spectroscopy (LC-MS) and gene expression (DNA microarray) measurements from the same samples, to identify genes controlling the production of metabolites. Due to the high dimensionality of both LC-MS and DNA microarray data, dimension reduction and variable selection are key elements of the analysis. Our proposed approach starts by identifying the basis functions ("building blocks") that constitute the output from a mass spectrometry experiment. Subsequently, the weights of these basis functions are related to the observations from the corresponding gene expression data in order to identify which genes are associated with specific patterns seen in the metabolite data. The modeling framework is extremely flexible as well as computationally fast and can accommodate treatment effects and other variables related to the experimental design. We demonstrate that within the proposed framework, genes regulating the production of specific metabolites can be identified correctly unless the variation in the noise is more than twice that of the signal.
authors.affiliation: Department of Mathematical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Kasper
authors.initials: K
authors.lastname: Brink-Jensen
authors.forename: Søren
authors.initials: S
authors.lastname: Bak
authors.forename: Kirsten
authors.initials: K
authors.lastname: Jørgensen
authors.forename: Claus Thorn
authors.initials: CT
authors.lastname: Ekstrøm
mesh_terms: D002853:Chromatography, Liquid; D013058:Mass Spectrometry; D055432:Metabolomics; D008954:Models, Biological; D020411:Oligonucleotide Array Sequence Analysis; D059467:Transcriptome